Translational studies of glutathione in bladder cancer cell lines and human specimens
Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration in the bladder cell lines was approximately 6-fold...
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Published in | Clinical cancer research Vol. 3; no. 5; pp. 793 - 798 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.05.1997
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Subjects | |
Online Access | Get full text |
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Summary: | Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon
and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration
in the bladder cell lines was approximately 6-fold higher than in the non-bladder cell lines. Because this difference suggested
the possibility of elevation of GSH in urothelial neoplasia, we measured GSH in bladder tumor tissue from patients with transitional
cell carcinoma (TCC) of the bladder (Group I, n = 17). GSH was also measured in two types of control tissues: (a) nontumor
bladder tissue from patients with TCC or a history of TCC of the bladder (Group II, n = 23); and (b) bladder tissue from patients
without bladder cancer (Group III, n = 14). Thirteen sets of paired specimens of tumor and nontumor bladder tissue from the
same patient were evaluated. The tissues were flash-frozen, and GSH was measured after histological assessment of the same
samples. Free and total GSH (free + mixed disulfides) were measured by a high-performance liquid chromatography assay with
fluorescence detection and expressed as nanomoles/mg protein. The mean free GSH (+/- SD) for groups I, II, and III was 32.0
+/-18.7, 17.3 +/- 11.4, and 9.3 +/- 4.0, respectively, and the mean total GSH was 45.9 +/- 32.5, 23.7 +/- 17.1, and 12.2 +/-
6.7. The respective differences between groups (I and II, I and III, and II and III) were statistically significant for both
free and total GSH (Ps ranging from <0.0001 to </=0.05). Free and total GSH were higher in tumor than in nontumor tissue in
11 of 13 paired specimens (free, 29.5 +/- 20.4 versus 18.7 +/- 11.7, P = 0.017; total, 41.7 +/- 33.8 versus 24.9 +/- 18.4,
P = 0.005). No correlation was found between GSH levels and the proportion of tumor cells in the tissue. Influence of smoking
on GSH expression could not be assessed because 81% of the patients with TCC had a smoking history. Similarly, because only
11% had prior cytotoxic chemotherapy, the influence of prior cytotoxic exposure on GSH could not be assessed. The results
indicate: (a) significantly higher levels of GSH in TCC compared to tumor-free bladder tissue; and (b) higher GSH levels in
nontumor bladder tissue from patients with bladder cancer than from patients without TCC. The clinical implications of this
work include the possibility that GSH may play a role in the resistance of bladder cancer to chemotherapy and may be associated
with bladder carcinogenesis. |
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ISSN: | 1078-0432 1557-3265 |